Early Response (Molecular and Cytogenetic) and Long-Term Outcomes in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Exploratory Analysis of DASISION 3-Year Data

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1675-1675 ◽  
Author(s):  
Giuseppe Saglio ◽  
Hagop M. Kantarjian ◽  
Neil Shah ◽  
Elias J. Jabbour ◽  
Alfonso Quintas-Cardama ◽  
...  
Keyword(s):  
Lower Risk ◽  
Research Funding ◽  
Clinical Importance ◽  
Early Response ◽  
Cytogenetic Response ◽  
Exploratory Analysis ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Molecular Analyses

Abstract Abstract 1675 Background: In the randomized phase 3 DASISION trial in patients (pts) with newly diagnosed CML-CP, dasatinib 100 mg once daily (QD) demonstrated improved efficacy over imatinib 400 mg QD and an acceptable tolerability profile (NEJM 2010 362 2260). At 3 years (y) pts achieved high rates of progression free survival (PFS) (91% both arms) and overall survival (OS) (94%, dasatinib; 93%, imatinib). Compared with pts receiving imatinib, pts receiving dasatinib achieved higher rates of cytogenetic and molecular responses, shorter time to responses, and fewer transformations to accelerated/blast phase (AP/BP) (JCO 2012 30 6504). Marin et al reported that BCR-ABL levels at 3 and 6 months (mo) with imatinib were significantly correlated with 8-y PFS and OS (JCO 2012 30 232), and Hanfstein et al proposed BCR-ABL levels of 10% at 3 mo and 1% at 6 mo as clinically important landmarks correlated with 5-y PFS and OS (Leukemia 2012 Epub). The aim of this exploratory analysis was to investigate the impact of early molecular and cytogenetic response on the outcome of pts enrolled in the DASISION trial. Methods: Pts with CML-CP were randomized to receive dasatinib 100 mg QD (n=259) or imatinib 400 mg QD (n=260). Methods have been previously reported (NEJM 2010 362 2260). PFS and OS rates were obtained from Kaplan-Meier estimates. Qualifying events for PFS included: increasing white blood cells, loss of complete hematologic response or major cytogenetic response, transformation to AP/BP, or death. Results: More dasatinib v imatinib pts achieved a partial cytogenetic response (PCyR) or complete CyR (CCyR) at 3 mo (81% v 67%) and at 6 mo (91% v 81%). Significantly higher rates of 3-y PFS were observed in pts with PCyR/CCyR at 3 mo (P<.0001, P=.0026 for dasatinib, imatinib) or at 6 mo (P=.0172, <.0001). Of pts with 3-mo molecular analyses (235 dasatinib, 239 imatinib), more pts treated with dasatinib achieved BCR-ABL ≤10% (84% v 64%) or ≤1% (48% v 13%). Of pts with 6-mo molecular analyses (236 dasatinib, 236 imatinib), more pts treated with dasatinib achieved BCR-ABL ≤10% (89% v 83%) or ≤1% (70% v 50%). Pts with BCR-ABL ≤10% at 3 mo had significantly better 3-y PFS (dasatinib: 93.1% v 68.2%, P=.0003; imatinib: 95.9% v 75.3%, P<.0001) and OS (dasatinib: 95.9% v 85.9%, P=.0348; imatinib: 96.0% v 88.0%, P=.0036). Pts with BCR-ABL ≤1% at 6 mo had significantly better PFS (dasatinib: 94.9% v 84.6%, P=.0020; imatinib: 97.4% v 83.8%, P=.0016) and with imatinib significantly better OS (97.4% v 93.6%, P=.0215). The difference between BCR-ABL ≤1% v >1–10% at 6 mo was not significant. Pts with BCR-ABL ≤10% and ≤1% at 3 and 6 mo had a lower risk of transformation within 3 y (Table); transformation was associated with a high risk of death (overall 50% mortality within 7 mo). In addition, pts receiving imatinib who had a poor response at 3 mo (BCR-ABL >10%) who achieved ≤10% at 6 mo still had a higher risk of transformation in comparison with those who achieved an initial deeper response at 3 mo. However, no patient on dasatinib with BCR-ABL >10% at 3 mo and ≤10% at 6 mo transformed. Conclusions: More pts treated with dasatinib achieved a faster, deeper cytogenetic and molecular response, which was associated with better 3-y outcomes and lower risk of transformation to AP/BP. The clinical importance of achieving deeper levels of cytogenetic response (CCyR) at 6 mo will be presented. Early response landmarks may identify pts at higher risk for transformation, poor outcome, and those who may benefit from alternate treatments to improve responses and thereby minimize exposure to risk over time. More pts starting on imatinib compared with dasatinib transformed to AP/BP than those receiving dasatinib. These exploratory data highlight the clinical importance of a fast and deep response, with the potential to reduce the risk of transformation and improve long-term outcomes. OS data at 3 y in DASISION are immature and longer-term follow up is planned. Disclosures: Saglio: Bristol-Myers Squibb: Consultancy, Speakers Bureau. Kantarjian:Bristol-Myers Squibb: Research Funding. Shah:Novartis: Consultancy; Bristol-Myers Squibb, Ariad: Consultancy, Research Funding. Jabbour:Bristol-Myers Squibb, Novartis: Honoraria; Pfizer: Consultancy. Quintas-Cardama:Bristol-Myers Squibb: Consultancy; Novartis: Consultancy. Steegmann:Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau. Boqué:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy. Chuah:Novartis, Bristol-Myers Squibb: Honoraria. Pavlovsky:Bristol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Mayer:Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Ukropec:Bristol-Myers Squibb: Employment. Wildgust:Bristol-Myers Squibb: Employment, Equity Ownership. Hochhaus:Pfizer, ARIAD, Bristol-Myers Squibb, Novartis: Research Funding; Pfizer, ARIAD, Bristol-Myers Squibb, MSD, Novartis: Consultancy.

Sustained Superior Long-Term Outcomes of Imatinib Therapy In Japanese Patients with Newly Diagnosed Chronic Myelogenous Leukemia In Chronic Phase: Sub-Analysis According to the Mean Daily Dose of Imatinib and the Plasma Trough Levels In JALSG CML202 Study After 66 Months Follow-up.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3417-3417
Author(s):  
Chiaki Nakaseko ◽  
Kazunori Ohnishi ◽  
Jin Takeuchi ◽  
Shin Fujisawa ◽  
Tadashi Nagai ◽  
...  
Keyword(s):  
Research Funding ◽  
Japanese Patients ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Daily Dose ◽  
The Mean

Abstract Abstract 3417 Background: Now, imatinib has been established as a first line therapy for the patients with chronic myelogenous leukemia (CML) in chronic phase (CP), and a standard initial dose is 400 mg daily. Although less than 300 mg showed unsatisfactory results, 300 mg or more appears effective in some patients intolerant to standard dose. However, large studies have not yet explored the response to lower dose of imatinib. In this CML202 study, although initial dose of imatinib was scheduled to be 400 mg, many patients actually received reduced dose mainly due to adverse events. However, overall efficacy and outcomes had been comparable to other studies. We performed subgroup analysis regarding long-term survivals according to the mean daily dose during the first 6 months, 12 months, and 24 months, respectively. We also measured imatinib plasma trough concentration (Cmin) in patients receiving imatinib at a dose of 300 mg or 400 mg, and compared efficacy and survivals between them. Methods: The prospective multicenter study of imatinib therapy in Japanese patients with newly diagnosed CML-CP was conducted in Japan Adult Leukemia Study Group (JALSG CML202 study). The objectives of this study were to determine the efficacy, safety and long-term outcomes of imatinib therapy in patients with newly diagnosed CML-CP. Primary end point of imatinib therapy was overall survival (OS). Initial daily dose of imatinib was 400 mg. The plasma concentration of imatinib was measured using liquid chromatography-tandem mass spectrometry. Results: 488 patients were enrolled between 2002 and 2006, and data at a median follow-up of 66 months were analyzed. The cumulative best response rates of major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and major molecular response (MMR) were 99%, 98% and 81%, respectively. At 66 months, the estimated rate of overall survival (OS) was 93% (95% CI, 90 to 96), and that of survival without progression to accelerated phase (AP) or blast crisis (BC) was 97% (95% CI, 96 to 99). In the landmark analysis at 12 months or 18 months according to the cytogenetic response or the molecular response, patients who had CCyR or MMR showed significantly better event free survival (EFS) rates than those who had not, respectively. Mean daily doses of imatinib administered during the first 24 months were 400 mg or more (400 mg group) in 294 patients, less than 400mg and 300mg or more (300 mg group) in 108 patients, and less than 300 mg (200 mg group) in 86 patients. The efficacy and outcomes at 66 months were evaluated according to the mean daily dose (400, 300, 200 mg group). The estimated rates of OS were 98%, 92% (P=0.09), and 74% (P<0.0001), and those of EFS were 91%, 79% (P=0.003), and 56% (P=0.0004), respectively. The estimated rates of survival without AP/BC were 99%, 97% (P=0.20), and 90% (P=0.03), respectively. OS, EFS and survival without AP/BC in 200 mg group were significantly inferior to those in 300 mg or more groups. OS and survival without AP/BC were not significantly different between 300 mg group and 400 mg group. However, EFS was significantly different between 300 mg group and 400 mg group. The cumulative CCyR and MMR rates in 200 mg group were inferior to those in 300 mg or more groups, however, they were not significantly different between 300 mg group and 400 mg group. OS and survivals without AP/BC in both 400 mg and 300 mg groups seem better as compared with the results of the IRIS study. However, EFS in 300 mg group was inferior to that of the IRIS study. The median (range) Cmin of imatinib in patients receiving 300 mg (n=24) and 400 mg (n=26) were 1,130 ng/mL (439-2,140) and 1,035 ng/mL (710-2,420), respectively. Cmin in patients receiving 300 mg distributed toward lower concentration as compared to those with 400 mg, even though they were not significantly different. Conclusion: The long-term results of the JALSG CML202 study revealed almost similar to those of the European countries in spite of the relatively lower mean daily dose. Imatinib at 400 mg or more induced excellent long-term outcomes in Japanese patients, however, EFS in 300 mg group was inferior to that in 400 mg group. These results suggest that higher daily dose is associated with better outcomes, however, imatinib at least 300 mg might be acceptable for patients intolerant to dose at 400 mg. Monitoring Cmin might be useful to find the optimal dose. Disclosures: Ohnishi: Novartis: Research Funding. Miyazaki:Novartis: Research Funding. Kiyoi:Novartis: Research Funding. Naoe:Novartis: Research Funding.

Reduction of BCR-ABL Transcript Levels at 6, 12, and 18 Months (mo) Correlates with Long-Term Outcomes on Imatinib (IM) at 72 Mo: An Analysis from the International Randomized Study of Interferon versus STI571 (IRIS) in Patients (pts) with Chronic Phase Chronic Myeloid Leukemia (CML-CP)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 334-334 ◽  
Author(s):  
Timothy P Hughes ◽  
Andreas Hochhaus ◽  
Susan Branford ◽  
Martin C Müller ◽  
Letizia Foroni ◽  
...  
Keyword(s):  
Cytogenetic Response ◽  
The Other ◽  
Molecular Response ◽  
Long Term Outcomes ◽  
First Line ◽  
Available N ◽  
Molecular Analyses ◽  
Over Time ◽  
Time Point

Abstract Background: An exploratory endpoint of the IRIS trial was measurement of BCR-ABL transcripts over time and its correlation with long-term outcomes. BCR-ABL measured by polymerase chain reaction (PCR) was required per protocol only after achievement of a complete cytogenetic response (CCyR). However, preplanned substudies occurred at sites in Germany and Australia who conducted PCR measurements on pts at intervals from the start of treatment independent of cytogenetic response (CyR). Additionally, other IRIS investigators contributed non-protocol specified molecular assessments. This first entire PCR dataset from IRIS assesses the prognostic value of molecular response (MR) at specific time points. Methods: 553 pts were enrolled onto the IM arm of IRIS; of these, 476 pts with at least one PCR measurement form the basis for this analysis. A major molecular response (MMR) is defined as the ratio of BCR-ABL/control gene (BAC) of ≤0.1%. Analyses were conducted at 6, 12 and 18 mo relating BAC percent reduction to event free survival (EFS), where events were defined as death during study treatment, loss of complete hematologic response, loss of Major CyR (MCyR), progression to accelerated phase (AP) or blast crisis (BC), or an increasing white blood cell count to &gt; 20 × 109/L. Results: Among pts receiving first line IM for CML-CP, MMR was observed in 13% of samples available for study at 3 mo, 33% at 6 mo, 50% at 12 mo, 65% at 18 mo, 75% at 48 mo, 85% at 60 mo, and 86% at 72 mo. The degree of molecular response in pts who achieved CCyR is described in Table 1. This exploratory analysis demonstrates close correlation between CCyR and BAC ≤1% at 6 months and beyond. Table 1. Correlation of CCyR with molecular response at 3, 6, 12 and 18 mo. Time point Pts with CCyR and PCR samples available (n) CCyR and ≤0.1% BAC [MMR], n (%) CCyR and ≤1% BAC, n (%) 3 mo 51 17 (33%) 38 (75%) 6 mo 127 61 (48%) 114 (90%) 12 mo 177 110 (62%) 168 (95%) 18 mo 163 127 (78%) 154 (94%) At 6 mo, half of the pts with BAC &gt;10% who also had a cytogenetic assessment at the same time had at least a partial cytogenetic response (PCyR) with an EFS of 91% at 72 mo, and 64% of these pts achieved MMR later. The other half of the pts with &gt;10% BAC who did not have a PCyR at 6 mo had an EFS of 43%, and 31% later achieved MMR. A separate landmark analysis by CyR status alone showed EFS rates at 72 mo of 92% for pts in CCyR, 86% for pts in PCyR, 60% for Minor/Minimal CyR and 49% for No CyR. At 12 mo, pts with BAC ≤ 1% had excellent long term outcomes (72 month EFS of &gt;90%, &gt;95% without progression to AP/BC). Those pts with BAC &gt; 1–≤ 10% (n = 36) had a 67% EFS, and 44% later achieved an MMR. These molecular analyses compare similarly to cytogenetic analyses alone (Baccarani et al; ASH 2006), with 60 mo EFS of 93% for pts in CCyR, 78% for pts in PCyR and 61% for pts without PCyR At 18 mo, pts with MMR could be statistically distinguished from pts with BAC &gt;0.1–≤ 1%; EFS was 98% versus 89%, p=0.0137 (with 6 events in each group). The rate without AP/BC at 72 mo was not significantly different (with only 2 events in the &gt;0.1 – ≤ 1% group). Baccarani et al (ASH 2006) reported an EFS at 60 mo of 96% for pts in CCyR, 80% for pts in PcyR and 69% for pts without PCyR. Table 2: Long-term outcomes (estimated rates at 72 mo) by MR levels at 6, 12 and 18 mo. BCR-ABL categories ≤0.1% (MMR) &gt;0.1 −≤1% &gt;1 −≤10% &gt;10% *P=.0137. None of the other comparisons between MMR and &gt; 0.1–≤1% BAC were statistically significant. 6 mo landmark N=86 N=89 N=44 N=39 EFS rate at 72 mo 90% 94% 88% 55% Without AP/BC at 72 mo 96% 100% 95% 74% 12 mo landmark N=153 N=90 N=36 N=26 EFS rate at 72 mo 94% 93% 67% 46% Without AP/BC at 72 mo 100% 96% 83% 76% 18 mo landmark N=164 N=48 N=25 N=16 EFS rate at 72 mo 98%* 89%* 67% 47% Without AP/BC at 72 mo 100% 96% 83% 82% Conclusion: In pts on first-line IM, MMR rates increase over time, and in pts who achieved an MMR at any time point progression is rare. Achievement of a CCyR correlated well with BAC of ≤1% from 6 mo onwards. Exploratory molecular analyses show pts with BAC &gt;10% at 6 mo have EFS rates distinguishable by their cytogenetic status. At 12 mo, pts with a BAC &gt; 1% or without CCyR, fare more poorly than those with BAC ≤ 1% or those in CCyR. At 18 mo pts with BAC ≤ 1% have excellent long term outcomes, with the best outcomes seen in those with BAC ≤ 0.1%. Molecular and cytogenetic evaluations are recommended until at least CCyR is achieved, with molecular assessments measured indefinitely thereafter.

ENESTnd Update: Nilotinib (NIL) Vs Imatinib (IM) In Patients (pts) With Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP) and The Impact Of Early Molecular Response (EMR) and Sokal Risk At Diagnosis On Long-Term Outcomes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 92-92 ◽  
Author(s):  
Giuseppe Saglio ◽  
Andreas Hochhaus ◽  
Timothy P. Hughes ◽  
Richard E. Clark ◽  
Hirohisa Nakamae ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Eligibility Criterion ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Vascular Events ◽  
Advisory Committees ◽  
The Impact

Abstract Introduction Frontline NIL continues to show benefit over IM in pts with Philadelphia chromosome-positive (Ph+) CML-CP, with higher rates of major molecular response (MMR; BCR-ABLIS ≤ 0.1%) and MR4.5 (BCR-ABLIS ≤ 0.0032%), lower rates of progression to accelerated phase (AP)/blast crisis (BC) and fewer new BCR-ABL mutations on treatment in the Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Pts (ENESTnd) trial. Here, we report data with a minimum follow-up (f/u) of 4 y; updated data based on 5 y of f/u will be presented. Methods Adults with newly diagnosed Ph+ CML-CP (N = 846) were randomized to NIL 300 mg twice daily (BID; n = 282), NIL 400 mg BID (n = 281), or IM 400 mg once daily (QD; n = 283). Progression and overall survival (OS) events were collected prospectively during study f/u, including after discontinuation of study treatment. Efficacy in the NIL 300 mg BID and IM arms was evaluated based on achievement of EMR (BCR-ABLIS ≤ 10% at 3 mo). Results At 4 y, ≥ 87% of pts remained on study in each arm and 57%-69% remained on core treatment (Table). Rates of MMR and MR4.5 by 4 y were significantly higher with NIL vs IM. Significantly fewer pts progressed to AP/BC on NIL vs IM (on core treatment: 0.7%, 1.1%, and 4.2%; on study: 3.2%, 2.1%, and 6.7% [NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively]). Of 17 pts across the 3 arms who progressed on core treatment, 11 (65%) had never achieved complete cytogenetic response and none had achieved MR4.5. Fewer mutations have emerged in the NIL arms vs the IM arm; in y 4, mutations emerged in 2 pts (1 pt with T315I on NIL 300 mg BID; 1 pt with F317L on IM). More pts achieved EMR in the NIL 300 mg BID arm vs the IM arm (91% vs 67%). Pts with EMR had significantly higher rates of progression-free survival (PFS) and OS at 4 y vs pts with BCR-ABL > 10% at 3 mo. Among pts with BCR-ABL > 10% at 3 mo, more progressions to AP/BC occurred in the IM arm (n = 14) vs the NIL 300 mg BID arm (n = 2); half of these pts progressed between 3 and 6 mo. In pts with intermediate or high Sokal risk, PFS and OS at 4 y were higher in both NIL arms vs the IM arm. No new safety signals were detected. Selected cardiac and vascular events were more common on NIL vs IM (by 4 y, peripheral arterial occlusive disease [PAOD] in 4 [1.4%], 5 [1.8%], and 0 pts; ischemic heart disease [IHD] in 11 [3.9%], 14 [5.1%,] and 3 [1.1%] pts; and ischemic cerebrovascular events in 3 [1.1%], 5 [1.8%], and 1 [0.4%] pts in the NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively). In the NIL 300 mg BID arm, 2 of 11 IHD events occurred between 3 and 4 y (all 4 PAOD events occurred in the first 2 y). In the NIL 400 mg BID arm, 2 of 5 PAOD events and 3 of 14 IHD events occurred between 3 and 4 y. Most pts (7 of 9) with a PAOD event on NIL were at high risk due to a combination of baseline risk factors. Conclusions NIL, a standard-of-care frontline therapy option for newly diagnosed CML-CP pts, affords superior efficacy compared with IM, including higher rates of EMR (which is associated with improved long-term outcomes), higher rates of MR4.5 (a key eligibility criterion for many studies of treatment-free remission), and a lower risk of disease progression. NIL continues to show good tolerability with long-term f/u. While selected cardiac and vascular events (including PAOD) are slightly more frequent on NIL vs IM, no increase in annual incidence of these events over time has been observed. Disclosures: Saglio: ARIAD: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Hochhaus:Ariad: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Hughes:Ariad: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CSL: Research Funding. Clark:Pfizer: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau. Nakamae:Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau, travel/ accomodations/ meeting expenses Other. Kim:BMS, Novartis,IL-Yang: Honoraria; Pfizer: Consultancy, Research Funding. Etienne:Pfizer: Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Flinn:Novartis: Research Funding. Lipton:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ariad: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Moiraghi:Bristol Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Fan:Novartis: Employment. Menssen:Novartis: Employment. Kantarjian:Novartis: Research Funding; Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; ARIAD: Research Funding. Larson:Pfizer: Consultancy; Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy.

Assessment Of Early Cytogenetic Response By 3 Months Versus >3-6 Months Or No Response By 6 Months As a Predictor Of Long-Term Clinical Outcomes In a Phase 1/2 Study Of Bosutinib In Chronic Phase CML

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1484-1484
Author(s):  
Jorge E. Cortes ◽  
H. Jean Khoury ◽  
Andreas Hochhaus ◽  
Jane F Apperley ◽  
Stephen G. O'Brien ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Research Funding ◽  
Phase 1 ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Rank Test ◽  
Long Term Outcomes ◽  
Line Therapy ◽  
Significant Difference

Abstract Bosutinib (BOS), an oral dual Src/Abl tyrosine kinase inhibitor (TKI), showed clinical activity and manageable toxicity in an open-label, phase 1/2 trial in patients (pts) with chronic phase (CP) chronic myeloid leukemia (CML) following resistance (R)/intolerance (I) to imatinib (IM) only (2nd line; CP2L) or to IM plus dasatinib (D) and/or nilotinib (N) (3rd/4th line; CP3L). In this retrospective analysis, a major cytogenetic response (MCyR) by 3 or by 6 mo (but not by 3 mo) was assessed as a predictor of long-term outcomes in CP2L or CP3L pts receiving BOS. CP-CML pts aged ≥18 y received BOS starting at 500 mg/d. MCyR and complete cytogenetic response (CCyR) rates and maintenance of MCyR were assessed in CP2L pts at 4 y and CP3L pts at 3 y. Pts with MCyR newly attained or maintained from baseline by 3 mo, by >3 to ≤6 mo (but not by 3 mo), or no MCyR by 6 mo were assessed for overall survival (OS) at 2 y (all pts) and cumulative incidence of progression (including lack of efficacy)/death at 4 y (CP2L) or 3 y (CP3L), adjusted for competing risks (see Table). OS rates were limited to 2 y (pts were followed for only 2 y from BOS discontinuation). P values were based on Gray's test for comparison of cumulative incidence distributions and log-rank test for OS distributions (no adjustment for multiple comparisons).Table.MCyR by 3 moMCyR by >3 to ≤6 moNo MCyRby ≤6 moCP2L ptsOSEvaluable pts,* n9628151KM rate at 2 y (95% CI), %98 (91.8–99.5)†96 (77.2–99.5)89 (82.1–92.7)Cumulative incidence of progression (including lack of efficacy)/death,‡ %Evaluable pts,µ n9026100Rate at 4 y (95% CI), %13 (7.9–22.7)†23 (11.4–46.6)40 (31.5–50.9)CP3L ptsOSEvaluable pts,* n281271KM rate at 2 y (95% CI), %89 (68.9–96.2)100 (Not estimable–100)84 (73.1–90.9)Cumulative incidence of progression (including lack of efficacy)/death,‡ %Evaluable pts,µ n241237Rate at 3 y (95% CI), %33 (18.9–58.7)25 (9.4–66.6)51 (37.5–70.3)*Pts known to be alive as of the 6-mo response landmark.†P≤0.0004 vs no MCyR by ≤6 mo (comparison of OS and cumulative incidence distributions, unadjusted [P≤0.0002] and adjusted [P≤0.0004] for pre-existing neutropenia and/or thrombocytopenia and presence of a baseline mutation).‡Adjusted for the competing risk of treatment discontinuation without progression/death.µPts known to be alive with no disease progression as of the 6-mo response landmark. CP2L pts (n=286 [IM-R, n=196; IM-I, n=90]) had a median (range) age of 53 (18–91) y. CP3L pts (n=118 with prior IM failure [D-R, n=38; D-I, n=50; N-R, n=26; N-I or D-R/I + N-R/I, n=4]) had a median (range) age of 56 (20–79) y. Median time from CML diagnosis was 3.7 (0.1–15.1) and 6.6 (0.6–18.3) y for CP2L and CP3L pts, respectively; BOS treatment duration was 24.8 (0.2–83.4) and 8.5 (0.2–78.1) mo; follow-up duration was 47.3 (0.6–90.6) and 33.1 (0.3–84.8) mo. Time from last enrolled pt's first dose to database snapshot was ≥48 mo for CP2L and ≥36 mo for CP3L. Of 264 CP2L pts with a valid baseline assessment, 107/183 (58%) IM-R and 49/81 (60%) IM-I pts attained/maintained a MCyR; 88/183 (48%) and 42/81 (52%) pts had CCyR. The Kaplan-Meier (KM) probability of maintaining MCyR at 4 y was 69% for IM-R and 86% for IM-I pts. Of 110 CP3L pts with valid assessment, overall MCyR and CCyR rates were 40% and 32%; the KM probability of maintaining MCyR at 3 y was 65%. There was no significant difference in OS or cumulative incidence of progression/death distribution between CP2L pts with MCyR by 3 mo vs by >3 to ≤6 mo; however, OS (P=0.0004) and cumulative incidence of progression/death (P=0.0002) distributions were significantly better for CP2L pts with MCyR by 3 mo vs no MCyR by 6 mo (Table). For CP3L pts, there was no significant difference in long-term outcomes between early response groups. In conclusion, in CP-CML pts receiving BOS as 2nd-line therapy following IM failure (CP2L), pts who attained/maintained a MCyR by 3 mo had better OS and a lower progression/death distribution vs pts without MCyR by 6 mo; no significant differences were observed between pts achieving MCyR by 3 mo vs by >3 to ≤6 mo, although pt number was low for late responders. There were no significant differences in outcomes for CP-CML pts receiving BOS as 3rd/4th-line therapy, regardless of when or if MCyR was achieved, although the number of pts with MCyR was low. These results suggest that pts not achieving a MCyR by 6 mo, particularly in the 2nd-line setting, may require alternative therapies if options with better likelihood of response are available. Disclosures: Cortes: Pfizer, Ariad, Teva: Consultancy; Novartis, Bristol Myers Squibb, Pfizer, Ariad, Teva: Research Funding. Hochhaus:Pfizer: Research Funding. Apperley:Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Pfizer, Ariad: Honoraria (not direct from company), Honoraria (not direct from company) Other. O'Brien:BMS: Consultancy, Honoraria, Research Funding; Ariad, Novartis, Pfizer: Research Funding. Leip:Pfizer Inc: Employment. Turnbull:Pfizer Inc: Employment. Conlan:Pfizer Inc: Employment. Kantarjian:Pfizer Inc: Research Funding. Brümmendorf:Patent on the use of imatinib and hypusination inhibitors: Patents & Royalties; Ariad: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb, Pfizer: Consultancy, Honoraria.

scholarly journals Differences in Presentation and Survival Outcomes for African American Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5647-5647 ◽  
Author(s):  
Nisha Joseph ◽  
Vikas A. Gupta ◽  
Craig C Hofmeister ◽  
Charise Gleason ◽  
Leonard Heffner ◽  
...  
Keyword(s):  
African American ◽  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Advisory Committees ◽  
Entire Cohort ◽  
Significant Difference

Abstract Background : Though the incidence of MM is two- to threefold higher in the African American (AA) population compared to Caucasians, reported long term outcomes are less favorable presumably due to inequities in access to healthcare. Little is known about the biology or disease presentation among AAs. We have conducted a retrospective analysis of our institutional data of 1000 patients treated with RVD induction therapy, specifically assessing differences in presentation, disease biology, and outcomes in AA patients. Methods: A total of 1000 newly diagnosed MM patients were treated with RVD induction therapy [R - 25 mg/day (days 1-14), V - 1.3 mg/m2 (days 1, 4 8, 11) and D - 40 mg once/twice weekly as tolerated every 21 days] from January 1st 2005 until August 31st 2016. Dose-adjustments were made based on the treating physician's discretion and patient tolerability. Demographic and outcomes data for the patients were obtained from our IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria. Results: Of the 1000 patients included in the analysis, 564 (56.4%) of patients were white (W), and 339 (33.9%) were AA, consistent with the demographic representation of the state of GA and our institutional referral population. Median age of this cohort was 61 years (range 16-83), 57 for AA patients (range, 24-83) compared to 62 (range, 16-81) in white patients, suggesting the onset is earlier among AA which has been previously reported in population based studies. Other notable characteristics include: 42.5%M/57.5% F for AA cohort and 61.7%M/38.3%F for white cohort. In regard to stage, AA: 73.9% stage I/II, 26.1% stage III; W: 77.1% stage I/II, 22.9% stage III, showing no difference in prognostic staging at presentation. There was no statistically significant difference in the presenting labs between AA and whites except for hemoglobin, with more AA patients presenting with Hgb≤9.9 g/dL (45.7% AA vs 32.5% W, p <.0001). In terms of prevalence of high-risk cytogenetics, there was no significant difference between the two cohorts in: complex karyotype 16% white/14.4% AA; t(14;16) 2.4% W/2.8% AA; t(4;14) 4.7% W/5.0% AA; t(11;14) 11.7% W/15.9% AA; or del1p 6.5%W/7.8%AA. However, there were significant differences found in the rates of: amp 1q 19.2% W/10.6% AA, (p<.0001), del13 28.3% W/19.6% AA (p=.003), and del17p 11.7% W/7.2% AA (p=.019), all three significantly less frequent in AAs. Median time to transplant for the entire cohort was 5 months (range, 1-124), and median time to best response was 3 months (range, 0-39). There was no significant difference in the number of patients who underwent ASCT (84% W vs 82% AA, p=.241), nor in ≥VGPR rates post-induction and 100 days post-ASCT: 69.9% W vs 64.5% AA (p=.056) and 88.1% W vs 86.7% in AA patients (p=.317), respectively. Median PFS for the entire cohort was 63 months, 62 months (54-69.9) for white patients versus 65 months (53-76.9) for AA patients (p=0.403). At a median follow up of 38 months, median OS has not yet been reached. Conclusions: This is the largest reported cohort of myeloma patients treated with RVD induction, with one-third of the patients representing the AA population. In our dataset, AAs are diagnosed 5 years younger, with lower hemoglobin at presentation and lower rates of amp1q, del13 and del17p when compared to whites. When offered the same induction regimen and opportunity for ASCT, AAs tend to experience the same survival benefits as their white counterparts. The lack of significant difference in PFS or OS suggests standardization and improved access to care could lead to better long-term outcomes in the AA population. Disclosures Hofmeister: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Heffner:Genentech: Research Funding; Pharmacyclics: Research Funding; ADC Therapeutics: Research Funding; Kite Pharma: Research Funding. Boise:AstraZeneca: Honoraria; Abbvie: Consultancy. Kaufman:BMS: Consultancy; Janssen: Consultancy; Karyopharm: Other: data monitoring committee; Abbvie: Consultancy; Roche: Consultancy. Lonial:Amgen: Research Funding. Nooka:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Outcomes by Cytogenetic and Molecular Response at 12 and 18 Months of Imatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) in the IRIS Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2138-2138
Author(s):  
Michele Baccarani ◽  
Francois Guilhot ◽  
Richard A. Larson ◽  
Stephen G. O’Brien ◽  
Brian J. Druker ◽  
...  
Keyword(s):  
Blast Crisis ◽  
Randomized Study ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Pcr Analysis ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Free Survival

Abstract Long term data is now available from the International Randomized Study of Interferon vs. STI571 (IRIS). We performed landmark analyses for pts on imatinib (IM) at 12 and 18 months (mos) (n=509 and n=480 respectively) and stratified for CCyR (Ph+ 0%), PCyR (Ph+ >0–35%) or No MCyR (Ph+ >35%) at both timepoints. Progression-free survival (PFS) included all progressions to accelerated phase or blast crisis during treatment with IM, whereas event-free survival (EFS) also included any loss of MCyR/CHR, increase in WBC and CML-unrelated deaths on treatment as events. Overall survival (OS) considered all deaths including those after discontinuation of IM and irrespective of whether pts went on to transplant. Outcomes in IM pts by cytogenetic response at 12 and 18 mos Estimated long-term outcomes at 60 mos (%) CcyR CcyR EFS PFS OS by 30 mos (%) by 60 mos (%) 12 mos landmark CCyR N = 350 93 97 95 – – PCyR N = 86 78 93 90 57 64 No MCyR N = 73 61 81 80 21 36 18 mos landmark CCyR N = 358 96 99 97 – – PCyR N = 66 80 90 90 38 50 No MCyR N = 56 69 83 82 11 27 Although the level of cytogenetic response was predictive for long-term outcomes, PFS and OS were not statistically significantly different between 12-mos CCyR and PCyR. Note that 64% of PCyR pts and 36% of pts without MCyR at 12 mos subsequently achieved CCyR. Using the 18-mos landmark, 50% of PCyR pts and 27% of pts without MCyR achieved CCyR at a later time. Long-term outcomes were evaluated based on available BCR-ABL transcript levels in pts with CCyR. A 3-log reduction from standardized baseline value in untreated pts was defined as a major molecular response (MMR). No pts who achieved both CCyR and MMR at 12 or 18 mos progressed to AP/BC by 60 mos. Approximately 5% of pts with CCyR but no MMR at 12 mos (p=0.007) and only 2% of CCyR pts without MMR at 18 mos (p=0.11) subsequently progressed. Of approximately 25% of CCyR pts with available PCR analysis who did not achieve MMR at 18 mos, about half did achieve MMR at a later time and their estimated EFS rate at 60 mths was 91%. At 60 mos, 69% of patients randomized to IM remained on treatment. Achievement of CCyR and MMR by 12 and 18 mos after start of IM in newly diagnosed CML-CP are predictive for favorable long-term outcomes. About 50% of pts in PCyR or CCyR at these time points eventually achieve CCyR and MMR, respectively, on continued IM treatment. The ability to identify patients who may be late responders should be further studied.

Molecular Response at 3 Months On Nilotinib Therapy Predicts Response and Long-Term Outcomes in Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia in Chronic Phase (CML-CP).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3292-3292 ◽  
Author(s):  
Susan Branford ◽  
Dong-Wook Kim ◽  
Simona Soverini ◽  
Enrico Gottardi ◽  
Lan Beppu ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Long Term Outcomes ◽  
Advisory Committees ◽  
Imatinib Resistance ◽  
Transcript Levels ◽  
Imatinib Resistant

Abstract Abstract 3292 Poster Board III-1 Background: Nilotinib is a potent and highly selective BCR-ABL kinase inhibitor, approved for the treatment of Philadelphia positive CML patients (pts) in CP or accelerated phase (CML-AP) who are resistant or intolerant to prior therapy including imatinib. A recent analysis demonstrated an association between BCR-ABL transcript levels at 3 months (mos) and response in pts treated with second-line tyrosine kinase inhibitors (Branford et al. Blood. 2008). This multi-center analysis was conducted to examine the association specifically between the initial molecular response to nilotinib with response and outcomes. Methods: CML-CP pts (N = 321) with imatinib resistance or intolerance were included and post-baseline BCR-ABL transcript levels were available for 294 patients. Intolerant pts also exhibited some degree of resistance to imatinib and were not eligible for the study if demonstrating major cytogenetic response (MCyR), the primary study endpoint. We aimed to determine if the initial molecular response to nilotinib could predict the response and outcome of patients with or without BCR-ABL mutations at baseline or those with imatinib resistance or intolerance. BCR-ABL transcript levels at 3 mos were used to perform a landmark analysis to assess the association between the initial molecular response and estimated probability of MCyR, major molecular response (MMR), and event-free survival (EFS) at 24 mos. Events were defined as loss of hematologic or cytogenetic response, progression to AP/BC, discontinuation due to progression or death. The analysis excludes patients who had already attained MCyR (n = 111) or MMR [BCR-ABL% (IS) ≤ 0.1%] (n = 28) or who had an event (n = 22) within the first 3 mos of therapy for each respective landmark analysis. Patients censored within the first 3 mos were also excluded. Patients were then grouped according to their level of BCR-ABL% (IS). Results: BCR-ABL% (IS) at 3 mos correlated with MCyR rates at 24 mos; pts with BCR-ABL% (IS) ≤ 10 had better probability of response compared with pts with BCR-ABL% (IS) > 10 (62% vs 35%, respectively). This difference in MCyR rate was most significant for pts with baseline mutations (60% vs 19%, P = .006) and those with imatinib resistance (63% vs 33%, P = 0.0007). A similar trend was observed for patients without baseline mutations (64% vs 47%) and imatinib intolerance (57% vs 40%). BCR-ABL% (IS) at 3 mos was highly predictive of MMR rates at 24 mos (Table). Pts with BCR-ABL% (IS) values > 0.1 - ≤ 1 had significantly higher probability (65%) of achieving MMR for all patient groups, whereas those with BCR-ABL% (IS) > 10 had estimated rates of 10% or less. The BCR-ABL% (IS) value at 3 mos was also found to correlate with EFS at 24 mos (Table). The estimated EFS rate at 24 mos was highest for pts with BCR-ABL% (IS) values of ≤ 1 at 3 mos for each patient group and ranged from 75% to 100%. Patients with BCR-ABL% (IS) values > 10 at 3 mos had the poorest outcome and the estimated EFS rates ranged from 36% for patients with baseline mutations to 57% for those without baseline mutations. Conclusion: BCR-ABL% (IS) at 3 mos predicts response and long-term outcomes of imatinib-resistant and intolerant pts regardless of baseline mutation status at 24 mos on nilotinib therapy. Rapid reduction of BCR-ABL may be important for optimal response and outcome. Pts whose BCR-ABL % (IS) levels decreased below 10% at 3 mos demonstrated a high probability of achieving MMR and MCyR at 24 mos. Pts who achieve early molecular response may also have an increased probability of improved long-term outcomes on nilotinib therapy, while pts with BCR-ABL% (IS) value > 10 at 3 mos may have poorer prognosis. Disclosures: Branford: Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Kim:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Wyeth: Research Funding. Haque:Novartis: Employment. Shou:Novartis: Employment. Woodman:Novartis: Employment. Kantarjian:Novartis: Research Funding. Radich:Novartis: Consultancy, Honoraria, Research Funding. Saglio:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Hughes:Bristol-Myers Squibb: Advisor, Honoraria, Research Funding; Novartis: Advisor, Honoraria, Research Funding. Hochhaus:Novartis: Research Funding.

scholarly journals Genetic Characteristics and Long-Term Outcomes of Korean Adult Patients with Ph-like Acute Lymphoblastic Leukemia Versus Non-Ph-like Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4087-4087
Author(s):  
Jae-Ho Yoon ◽  
Hanwool Cho ◽  
Seug Yun Yoon ◽  
Gi June Min ◽  
Sung-Soo Park ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Genetic Characteristics ◽  
Ras Mutations

Abstract Background: Recently, a high-risk subgroup of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) called Philadelphia chromosome (Ph)-like ALL was identified in adolescents and young adults. However, there are conflicting data regarding the incidence and prognosis of Ph-like ALL in adult patients, and no data have yet been introduced in Asian countries. Aim: We tried to identify the prevalence and genetic characteristics of Ph-like ALL in adult patients with newly diagnosed BCP-ALL. Furthermore, we analyzed the clinical characteristics, long-term outcomes, and prognostic impact of Ph-like ALL compared with non-Ph-like ALL (Ph-positive ALL or BCP-other ALL). Methods: Between December 2008 and March 2016, 334 adult patients with newly diagnosed BCP-ALL who received modified hyper-CVAD chemotherapy and had suitable material for genomic analysis were included in this analysis (median age, 43 years [range, 16-65 years]). Our post-remission therapy was based on allogeneic hematopoietic cell transplantation (HCT) if a donor is available. Ph-like ALL was determined by next generation sequencing using the Archer® FusionPlex® ALL Kit (ArcherDX Inc., CO) which can detect fusions, point mutations, and expression levels in 81 genes associated with ALL and additional FISH analysis was done. Results: Overall, 48 (14.4%) of the 334 patients were Ph-like ALL, and the cohort was divided into patients with ABL1-class rearrangements (n=4), CRLF2 rearrangements (n=11), JAK2 rearrangements (n=4), other JAK-STAT sequence mutations (n=12), and RAS mutations (n=17). The remaining 286 patients had Ph-positive ALL (n=197) and BCP-other ALL (n=89; including 19 patients with KMT2A [MLL] rearrangements). No significant differences in baseline characteristics were observed between the Ph-like ALL and BCP-other ALL subgroups, whereas patients with Ph-positive ALL were older (median age, 47 vs 37 years; p=0.003) and had higher presenting leukocyte counts (median, 33.1 vs 11.4´109/L; p=0.001) compared with Ph-like ALL. The complete remission rate was somewhat different between the 3 disease subgroups (Ph-like ALL, 97.9%; Ph-positive ALL, 95.9%; BCP-other ALL, 88.8%; p=0.027). A higher proportion of patients with Ph-like ALL actually received allogeneic HCT in CR1 than patients with non-Ph-like ALL (Ph-like ALL, 91.6%; Ph-positive ALL, 84.2%; BCP-other ALL, 71.9%; p=0.007). With a median follow-up of 58.1 months (range; 6.0-121.0), outcomes of patients with Ph-like ALL were not inferior compared with outcomes of patients with non-Ph-like ALL. Disease-free survival rates at 5 years were 56.0% for Ph-like ALL, 42.6% for Ph-positive ALL, and 40.6% for BCP-other ALL (p=0.138). The 5-year cumulative incidence of relapse were 19.2% for Ph-like ALL, 35.3% for Ph-positive ALL, and 33.5% for BCP-other ALL (p=0.076). These findings were maintained when only patients receiving HCT were considered. Within the Ph-like ALL subgroup, patients with ABL1-class and CRLF2-rearrangements had worse outcomes than patients with other JAK-STAT sequence and RAS mutations. Also, patients with higher CRLF2 expression had inferior outcomes. Conclusion: Within the limitation of sample size, our data showed a different frequency of subtypes (e.g., lower incidence of CRLF2 rearrangements, higher RAS mutations) and treatment outcomes of adult patients with Ph-like ALL compared with other Western reports. Racial and ethnic differences in the patient population studied may have contributed to these differences. We also suggest that HCT-based post-remission therapy may overcome the poor prognosis of Ph-like ALL. Disclosures Kim: BMS: Research Funding; Ilyang: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Lee:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

scholarly journals Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis

Leukemia ◽  
2021 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Timothy P. Hughes ◽  
Richard A. Larson ◽  
Dong-Wook Kim ◽  
Surapol Issaragrisil ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Chronic Phase ◽  
Individual Treatment ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Treatment Free Remission

AbstractIn the ENESTnd study, with ≥10 years follow-up in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, nilotinib demonstrated higher cumulative molecular response rates, lower rates of disease progression and CML-related death, and increased eligibility for treatment-free remission (TFR). Cumulative 10-year rates of MMR and MR4.5 were higher with nilotinib (300 mg twice daily [BID], 77.7% and 61.0%, respectively; 400 mg BID, 79.7% and 61.2%, respectively) than with imatinib (400 mg once daily [QD], 62.5% and 39.2%, respectively). Cumulative rates of TFR eligibility at 10 years were higher with nilotinib (300 mg BID, 48.6%; 400 mg BID, 47.3%) vs imatinib (29.7%). Estimated 10-year overall survival rates in nilotinib and imatinib arms were 87.6%, 90.3%, and 88.3%, respectively. Overall frequency of adverse events was similar with nilotinib and imatinib. By 10 years, higher cumulative rates of cardiovascular events were reported with nilotinib (300 mg BID, 16.5%; 400 mg BID, 23.5%) vs imatinib (3.6%), including in Framingham low-risk patients. Overall efficacy and safety results support the use of nilotinib 300 mg BID as frontline therapy for optimal long-term outcomes, especially in patients aiming for TFR. The benefit-risk profile in context of individual treatment goals should be carefully assessed.

scholarly journals Prognostic analysis for short - and long-term outcomes of newly diagnosed epilepsy

Seizure ◽  
2017 ◽  
Vol 47 ◽  
pp. 92-98 ◽  
Author(s):  
Yong-li Jiang ◽  
Fang Yuan ◽  
Fang Yang ◽  
Xiao-long Sun ◽  
Xi-ai Yang ◽  
...  
Keyword(s):  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Prognostic Analysis ◽  
Short And Long Term
Sign in / Sign up

Export Citation Format

Share Document